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Chemical Structure| 321-14-2 Chemical Structure| 321-14-2
Chemical Structure| 321-14-2

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5-Chloro-2-hydroxybenzoic acid

CAS No.: 321-14-2

4.5 *For Research Use Only !

Cat. No.: A809692 Purity: 98%

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Schumacher, Tanner J ; Iyer, Ananth V ; Rumbley, Jon , et al.

Abstract: Background: Cancer cells alter their metabolic phenotypes with nutritional change. Single agent approaches targeting mitochondrial metabolism in cancer have failed due to either dose limiting off target toxicities, or lack of significant efficacy in vivo. To mitigate these clinical challenges, we investigated the potential utility of repurposing FDA approved mitochondrial targeting anthelmintic agents, niclosamide, IMD-0354 and pyrvinium pamoate, to be combined with GLUT1 inhibitor BAY-876 to enhance the inhibitory capacity of the major metabolic phenotypes exhibited by tumors. Methods: To test this, we used breast cancer cell lines MDA-MB-231 and 4T1 which exhibit differing basal metabolic rates of glycolysis and mitochondrial respiration, respectively. Metabolic characterization was carried out using Seahorse XFe96 Bioanalyzer and statistical analysis was carried out via ANOVA. Results: Here, we found that specific responses to mitochondrial and glycolysis targeting agents elicit responses that correlate with tested cell lines basal metabolic rates and fuel preference, highlighting the potential to cater metabolism targeting treatment regimens based on specific tumor nutrient handling. Inhibition of GLUT1 with BAY-876 potently inhibited glycolysis in both MDA-MB-231 and 4T1 cells, and niclosamide and pyrvinium pamoate perturbed mitochondrial respiration that resulted in potent compensatory glycolysis in the cell lines tested. Conclusion: In this regard, combination of BAY-876 with both mitochondrial targeting agents resulted in inhibition of compensatory glycolysis and subsequent metabolic crisis. These studies highlight targeting tumor metabolism as a combination treatment regimen that can be tailored by basal and compensatory metabolic phenotypes.

Keywords: Drug repurposing ; Anthelmintic ; BAY-876 ; Niclosamide ; Pyrvinium ; Anticancer

Purchased from AmBeed: ;

Tanner J. Schumacher ; Ananth V. Iyer ; Jon Rumbley , et al.

Abstract: Cancer cells alter their metabolic phenotypes with nutritional change. Single agent approaches targeting mitochondrial metabolism in cancer have failed due to either dose limiting off target toxicities, or lack of efficacy in vivo. To mitigate these clinical challenges, we investigated the potential utility of repurposing FDA approved mitochondrial targeting anthelmintic agents, niclosamide and pyrvinium pamoate, to be combined with GLUT1 inhibitor BAY-876 to enhance the inhibitory capacity of the major metabolic phenotypes exhibited by tumors. To test this, we used breast cancer cell lines MDA-MB-231 and 4T1 which exhibit differing basal metabolic rates of glycolysis and mitochondrial respiration, respectively. Here, we found that specific responses to mitochondrial and glycolysis targeting agents elicit responses that correlate with tested cell lines basal metabolic rates and fuel preference, highlighting the potential to cater metabolism targeting treatment regimens based on specific tumor nutrient handling. Inhibition of GLUT1 with BAY-876 potently inhibited glycolysis in both MDA-MB-231 and 4T1 cells, and niclosamide and pyrvinium pamoate perturbed mitochondrial respiration that resulted in potent compensatory glycolysis in the cell lines tested. In this regard, combination of BAY-876 with both mitochondrial targeting agents resulted in inhibition of compensatory glycolysis and subsequent metabolic crisis. These studies warrant further investigation into targeting tumor metabolism as a combination treatment regimen that can be tailored by basal and compensatory metabolic phenotypes.

Purchased from AmBeed: ;

Product Details of [ 321-14-2 ]

CAS No. :321-14-2
Formula : C7H5ClO3
M.W : 172.57
SMILES Code : O=C(O)C1=CC(Cl)=CC=C1O
MDL No. :MFCD00002457
InChI Key :NKBASRXWGAGQDP-UHFFFAOYSA-N
Pubchem ID :9447

Safety of [ 321-14-2 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301
Precautionary Statements:P264-P270-P301+P310+P330-P405-P501
Class:6.1
UN#:2811
Packing Group:

Calculated chemistry of [ 321-14-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 40.43
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

57.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.09
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

3.09
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.74
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.59
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.38
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.78

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.19
Solubility 0.11 mg/ml ; 0.000639 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.97
Solubility 0.0187 mg/ml ; 0.000108 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-1.81
Solubility 2.69 mg/ml ; 0.0156 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.16 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.56

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.18

Application In Synthesis [ 321-14-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 321-14-2 ]

[ 321-14-2 ] Synthesis Path-Downstream   1~22

  • 1
  • [ 13589-72-5 ]
  • [ 321-14-2 ]
  • 3
  • [ 321-14-2 ]
  • [ 320-72-9 ]
  • 4
  • [ 7647-18-9 ]
  • [ 69-72-7 ]
  • [ 321-14-2 ]
  • [ 320-72-9 ]
  • 5
  • [ 7647-01-0 ]
  • [ 7732-18-5 ]
  • [ 7722-84-1 ]
  • [ 69-72-7 ]
  • [ 321-14-2 ]
  • [ 320-72-9 ]
  • 6
  • [ 64-17-5 ]
  • [ 7782-50-5 ]
  • [ 69-72-7 ]
  • [ 321-14-2 ]
  • [ 320-72-9 ]
  • 7
  • [ 7782-50-5 ]
  • [ 64-19-7 ]
  • [ 69-72-7 ]
  • [ 321-14-2 ]
  • [ 320-72-9 ]
  • 8
  • [ 7782-50-5 ]
  • [ 69-72-7 ]
  • CS2 [ No CAS ]
  • [ 321-14-2 ]
  • [ 320-72-9 ]
  • 9
  • [ 7664-93-9 ]
  • [ 13589-72-5 ]
  • [ 321-14-2 ]
  • 10
  • dipotassium salicylate [ No CAS ]
  • [ 321-14-2 ]
  • [ 320-72-9 ]
  • 11
  • monopotassium salicylate [ No CAS ]
  • [ 321-14-2 ]
  • [ 320-72-9 ]
  • 12
  • [ 7732-18-5 ]
  • [ 578-36-9 ]
  • [ 7782-50-5 ]
  • [ 321-14-2 ]
  • [ 320-72-9 ]
  • 13
  • [ 321-14-2 ]
  • [ 349-58-6 ]
  • C15H7ClF6O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
13.9% With trichlorophosphate; In xylene; at 140℃; for 2h; A mixture of 5-chlorosalicylic acid(172.6mg, 1mmol), 3,5-bis(trifluoromethyl)phenol(152 muL, 1mmol), phosphorus oxychloride(40 muL, 0.43mmol) and xylene(3mL) was stirred at 140°C for 2 hours. After the reaction mixture was cooled to room temperature, it was poured into water and extracted with ethyl acetate. After the ethyl acetate layer was washed with brine and dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel(n-hexane:ethyl acetate=10:1-->5:1) to give the title compound(53.6mg, 13.9percent) as a white crystal.1H-NMR(CDCl3): delta 7.04(1H, d, J=9.0Hz), 7.54(1H, dd, J=9.0, 2.7Hz), 7.75(2H, s), 7.86(1H, s), 8.02(1H, d, J=2.7Hz), 10.09(1H, s).
13.9% With trichlorophosphate; In xylene; at 140℃; for 2h; A mixture of 5-chlorosalicylic acid(172.6mg, 1mmol), 3,5-bis(trifluoromethyl)phenol(152 muL, 1mmol), phosphorus oxychloride(40 muL, 0.43mmol) and xylene(3mL) was stirred at 140°C for 2 hours. After the reaction mixture was cooled to room temperature, it was poured into water and extracted with ethyl acetate. After the ethyl acetate layer was washed with brine and dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel(n-hexane:ethyl acetate=10:1-->5:1) to give the title compound(53.6mg, 13.9percent) as a white crystal.1H-NMR(CDCl3): delta 7.04(1H, d, J=9.0Hz), 7.54(1H, dd, J=9.0, 2.7Hz), 7.75(2H, s), 7.86(1H, s), 8.02(1H, d, J=2.7Hz), 10.09(1H, s).
13.9% With trichlorophosphate; In xylene; at 140℃; for 2h; A mixture of 5-chlorosalicylic acid(172.6mg, 1mmol), 3,5-bis(trifluoromethyl)phenol(152 muL, 1mmol), phosphorus oxychloride(40 muL, 0.43mmol) and xylene(3mL) was stirred at 140°C for 2 hours. After the reaction mixture was cooled to room temperature, it was poured into water and extracted with ethyl acetate. After the ethyl acetate layer was washed with brine and dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel(n-hexane:ethyl acetate=10:1-->5:1) to give the title compound(53.6mg, 13.9percent) as a white crystal.1H-NMR(CDCl3): delta 7.44(1H, d, J=9.0Hz), 7.54(1H, dd, J=9.0, 2.7Hz), 7.75(2H, s), 7.86(1H, s), 8.02(1H, d, J=2.7Hz), 10.09(1H, s).
13.9% With trichlorophosphate; In xylene; at 140℃; for 2h; A mixture of 5-chlorosalicylic acid(172.6mg, 1mmol), 3,5-bis(trifluoromethyl)phenol(152 muL, 1mmol), phosphorus oxychloride(40 muL, 0.43mmol) and xylene(3mL) was stirred at 140°C for 2 hours. After the reaction mixture was cooled to room temperature, it was poured into water and extracted with ethyl acetate. After the ethyl acetate layer was washed with brine and dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel(n-hexane:ethyl acetate=10:1-->5:1) to give the title compound(53.6mg, 13.9percent) as a white crystal.1H-NMR(CDCl3): delta 7.04(1H, d, J=9.0Hz), 7.54(1H, dd, J=9.0, 2.7Hz), 7.75(2H, s), 7.86(1H, s), 8.02(1H, d, J=2.7Hz), 10.09(1H, s).

  • 14
  • [ 58929-72-9 ]
  • [ 321-14-2 ]
  • [ 521065-04-3 ]
YieldReaction ConditionsOperation in experiment
93% With potassium carbonate; In ethyl acetate; acetonitrile; Example 65 6-[5-CHLORO-2-(2-METHOXY-ETHOXY)-PHENYL]-N-(4-CHLORO-PHENYL)[1,3,5]TRIAZINE-2,4-DIAMINE A mixture of 5-chlorosalicylic acid (5.0 g, 29.0 mmol), potassium carbonate (10.8 g, 78.1 mmol), acetonitrile (100 ml), and 2-bromoethylmethyl ether (6.8 ml, 72.3 mmol) was heated under reflux for 20 hours. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (50 ml). The solution was washed with aqueous sodium hydroxide solution (1 M, 2*50 ml), washed with water (50 ml), dried over sodium sulfate, and concentrated under reduced pressure to provide 5-chloro-2-(2-methoxyethoxy)benzoic acid 2-methoxyethyl ester (7.83 g, 93% yield).
  • 15
  • [ 321-14-2 ]
  • [ 3535-88-4 ]
  • 5-chloro-N-[5-(1,1-dimethyl)ethyl-2-methoxyphenyl]-2-hydroxybenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
89.5% Example 161 5-Chloro-N-[5-(1,1-dimethyl)ethyl-2-methoxyphenyl]-2-hydroxybenzamide (Comopund No. 160). Using 5-chlorosalicylic acid and 5-[(1,1-dimethyl)ethyl]-2-methoxyaniline as the raw materials, the same operation as the example 16 gave the title compound. Yield: 89.5%. 1H-NMR(DMSO-d6): δ 1.28(9H, s), 3.33(3H, s), 7.01(1H, d, J=8.7Hz), 7.05(1H, d, J=9.0Hz), 7.11(1H, dd, J=8.7, 2.4Hz), 7.47(1H, dd, J=9.0, 3.0Hz), 7.99(1H, d, J=3.0Hz), 8.49(1H, d, J=2.4Hz), 10.78(1H, s), 12.03(1H, s).
  • 16
  • [ 321-14-2 ]
  • [ 54396-44-0 ]
  • 5-chloro-2-hydroxy-N-[2-methyl-3-(trifluoromethyl)phenyl]benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
14.5% Example 118 5-Chloro-2-hydroxy-N-[2-methyl-3-(trifluoromethyl)phenyl]benzamide (Comopund No. 118). Using 5-chlorosalicylic acid and <strong>[54396-44-0]2-methyl-3-(trifluoromethyl)aniline</strong> as the raw materials, the same operation as the example 16 gave the title compound. Yield: 14.5percent. 1H-NMR(DMSO-d6): delta 2.36(3H, d, J=1.2Hz), 7.05(1H, d, J=8.7Hz), 7.46(1H, t, J=8.1Hz), 7.50(1H, dd, J=8.7, 2.7Hz), 7.60(1H, d, J=7.2Hz), 7.99(1H, d, J=7.2Hz), 8.00(1H, d, J=2.4Hz), 10.43(1H, s), 12.08(1H, s).
With pyridine; phosphorus trichloride; In toluene; for 12h;Inert atmosphere; Reflux; General procedure: The salicylic acid (1.2 equiv) was added to a mixture of toluene (0.3 M), aniline (1.0 equiv), phosphorus trichloride (1.1 equiv), and pyridine (0.05 equiv) in a Radley?s Carousel reaction tube (modified from Itai et al.20). The mixture was refluxed under nitrogen for 12 h then cooled to room temperature. Aqueous sodium bicarbonate was added dropwise to attain pH 6?7. The resultant mixture was extracted with EtOAc. The organic extracts were combined, dried (MgSO4), and concentrated under vacuum. After chromatography (1:10 EtOAc:Hex) compounds were recrystallized (EtOAc/Hex).
  • 17
  • [ 321-14-2 ]
  • [ 7149-75-9 ]
  • [ 860001-25-8 ]
  • 18
  • [ 321-14-2 ]
  • [ 5369-19-7 ]
  • [ 634186-63-3 ]
YieldReaction ConditionsOperation in experiment
89.9% With phosphorus trichloride; In 5,5-dimethyl-1,3-cyclohexadiene; dichloromethane;Reflux; Example 5 N-(3-tert-butylphenyl)-5-chloro-2-hydroxybenzamide (3i) Using the method described for compound 3a, 5-chlorosalicylic acid (2.04 g, 11.82 mmol) reacted with <strong>[5369-19-7]3-tert-butylaniline</strong> (1.76 g, 11.82 mmol) and 2M PCl3 in CH2Cl2 (2.336 mL, 4.73 mmol) in xylenes (30 mL). At completion of reaction, the hot xylenes solvent was decanted, cooled to room temperature, and then diluted with hexanes (30 mL). This was stored at 4° C. for 30 hours during which time an off-white crystalline solid separated. The product was recrystallized from EtOAc/hexanes to give a mixture of the title compound (89.9percent and an unidentified impurity (10.1percent). 1H NMR of the major component (400 MHz, DMSO-d6) delta 1.280 (S, 9H), 7.172 (dq, J=8.0, 0.8 Hz, 1H), 7.283 (dd, J=8.0, 0.8 Hz, 1H), 7.455 (dd, J=8.8, 2.6 Hz-, 1H), 7.560 (dd, J=8.0, 0.8 Hz, 1H), 7.679 (M, 1H), 7.982 (d, J=2.6 Hz, 1H), 10.345 (S, 1H), 11.903 (S, 1H). HPLC TR 3.095 min; m/z 303.95 [M+H]+; m/z- =301.85[M-H]-; (EM 303.10).
  • 19
  • [ 321-14-2 ]
  • [ 367-34-0 ]
  • [ 1417658-27-5 ]
YieldReaction ConditionsOperation in experiment
10% With pyridine; phosphorus trichloride; In toluene; for 12h;Inert atmosphere; Reflux; General procedure: The salicylic acid (1.2 equiv) was added to a mixture of toluene (0.3 M), aniline (1.0 equiv), phosphorus trichloride (1.1 equiv), and pyridine (0.05 equiv) in a Radley?s Carousel reaction tube (modified from Itai et al.20). The mixture was refluxed under nitrogen for 12 h then cooled to room temperature. Aqueous sodium bicarbonate was added dropwise to attain pH 6?7. The resultant mixture was extracted with EtOAc. The organic extracts were combined, dried (MgSO4), and concentrated under vacuum. After chromatography (1:10 EtOAc:Hex) compounds were recrystallized (EtOAc/Hex).
  • 20
  • [ 69-72-7 ]
  • [ 321-14-2 ]
  • [ 320-72-9 ]
  • [ 1829-32-9 ]
  • 21
  • [ 29608-05-7 ]
  • [ 321-14-2 ]
  • 5-chloro-2-hydroxy-N-(4-(piperidin-1-ylmethyl)phenyl)benzamide [ No CAS ]
  • 22
  • [ 7749-47-5 ]
  • [ 321-14-2 ]
  • C7H5ClO3*C6H9N3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol; for 0.5h;Heating; General procedure: The title salts were synthesized by the reaction of 1:1 stoichiometricmixtures of 2-amino-4-methoxy-6-methylpyrimidine(34.79 mg, 0.25 mmol) with 4-aminosalicylic acid (38.28 mg,0.25 mmol) or 5-chlorosalicylic acid (43.14 mg, 0.25 mmol) inhot methanol solution (20 ml), after warming over a water bathfor 30 min. The solutions were cooled and kept at roomtemperature.Within a few days, block-shaped brown crystals ofsalt I and colourless needle-shaped crystals of salt II wereobtained by slow evaporation at room temperature. Bothcrystals were suitable for single-crystal X-ray structure analysis
 

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